Tumor targeting of functionalized quantum dot-liposome hybrids by intravenous administration

Al-Jamal, Wafa T, Al-Jamal, Khuloud T, Tian, Bowen, Cakebread, Andrew, Halket, John M and Kostarelos, Kostas (2009) Tumor targeting of functionalized quantum dot-liposome hybrids by intravenous administration. Molecular Pharmaceutics, 6 (2). pp. 520-30. ISSN 1543-8384

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Abstract

A strategy to target functionalized quantum dot-liposome (f-QD-L) hybrid vesicles in the solid tumor tissue of tumor-bearing mice is explored. Functionalized polyethylene glycol (PEG)-lipid coated QD (f-QD) were encapsulated into the aqueous core of 100 nm cationic (DOPC:Chol: DOTAP); sterically stabilized, fluid-phase (DOPC:Chol:DSPE-PEG2000); and sterically stabilized, gel-phase (DSPC:Chol:DSPE-PEG2000) liposome vesicles. Double tracking of f-QD-L in blood was performed at different time points after intravenous administration in B16F10 melanoma tumor-bearing C57BL6 mice. Cholesteryl [-1-14C] oleate lipids probed the vesicle membrane were followed by liquid scintillation counting while QD were determined independently by elemental (Cd2+) analysis using inductively coupled plasma mass spectrometry (ICP-MS). Rapid blood clearance was observed following intravenous administration of the cationic hybrid vesicles, while incorporation of PEG at the surface of zwitterionic vesicles dramatically prolonged their blood circulation half-life after systemic administration. The "rigid" PEGylated f-QD-L (DSPC:Chol:DSPE-PEG2000) hybrid vesicles led to rapid tumor accumulation of peak values (approximately 5% of injected dose per gram tissue) of QD compared to long-circulating f-QD that accumulated in the tumor tissue at longer time points. More interestingly, this hybrid vesicle tumor retention persisted for at least 24 h. For almost all types of systems, a preferential cadmium uptake by liver and spleen was obtained. Overall, f-QD-L hybrid vesicles offer great potential for tumor imaging applications due to their rapid accumulation and prolonged retention within the tumor. Furthermore, f-QD-L offer many opportunities for the development of combinatory therapeutic and imaging (theranostic) modalities by incorporating both drug molecules and QD within the different compartments of a single vesicle.

Item Type: Article
Uncontrolled Keywords: animals,quantum dots,antineoplastic agents,lipids,melanoma, experimental,mice, inbred c57bl,mice,tissue distribution,polyethylene glycols,nanoparticles,liposomes,drug carriers
Faculty \ School: Faculty of Science > School of Pharmacy
Depositing User: Pure Connector
Date Deposited: 05 Oct 2013 00:56
Last Modified: 21 Apr 2020 21:57
URI: https://ueaeprints.uea.ac.uk/id/eprint/43581
DOI: 10.1021/mp800187d

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